The goal of the present project is to examine the neural basis of food motivation in Prader-Willi syndrome (PWS). The specific focus of this project will be to identify if overeating in PWS is caused not only by abnormal satiety response but also by abnormally heightened responses to rewarding food during hunger and after attempted satiation. PWS is characterized by an insatiable appetite associated with excessive overeating, propensity to obesity, food preoccupations, food foraging, and compulsivity. Previous studies suggest the PWS eating disorder is caused by an abnormally delayed satiety response as indicated by increased brain activation in the frontal and limbic regions of the brain implicated in appetite regulation. However, individuals with PWS also show clear preference for foods based on their taste and macronutrient content, typically favoring tasty high-fat or carbohydrate foods to foods with lower caloric values. The specific aims of the present project are (1) to delineate potential differences in neural response to food stimuli of varying caloric value during fasting and post-meal states in individuals with PWS and individuals matched to PWS on body mass index, age, and gender, and (2) to determine the relation between this neural activity and body mass index, food preference, severity of food-related problems, and compulsivity. These goals will be accomplished by conducting a two-part fMRI scan using a food/object discrimination task performed while hungry and after ingestion of a standardized uniform meal, and by collecting behavioral data on food-related problems and compulsivity. The proposed research should give insight into the underlying neural mechanisms of overeating in PWS and provide a basis for the development of treatments to counteract the eating disorder in the PWS population. In addition, since PWS is the leading known genetic cause of obesity, it is possible that what is learned about overeating and food motivation in PWS will reveal the mechanisms of obesity and appetite regulation in the general population. Information generated by the proposed research will allow an understanding of the underlying neural basis of the eating disorder that is characteristic of Prader-Willi syndrome. In addition, the project will further the understanding of the relationships between food preoccupations, compulsivity and neural mechanisms of hunger and satiety. The information gained may facilitate the development of targeted therapeutic interventions, both pharmacological and behavioral, and provide insight into the neural basis of appetite regulation that may be relevant to any individual struggling with obesity.